Regulation of meiotic arrest by a Gs-linked receptor

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DESCRIPTION (provided by applicant): The mammalian ovarian follicle presents a remarkable example of how cells communicate to regulate the cell cycle within a complex tissue. In particular, the somatic cells that surround the oocyte send a signal to the oocyte that maintains meiotic prophase arrest, and then in response to luteinizing hormone (LH), these same somatic cells send an opposite signal, causing meiosis to resume. Recent work from this laboratory has shown that the maintenance of prophase arrest requires the activity of a heterotrimeric G protein of the Gs family, and a Gs-linked receptor, GPR3, both located in the oocyte. The proposed studies will investigate the function of GPR3 in maintaining prophase arrest, as well as in restarting the meiotic cell cycle. Aim one is to examine the expression of Gpr3 during oogenesis, to further characterize the phenotype of a Gpr3 knockout mouse, and to determine whether the Gpr3 requirement for the maintenance of meiotic arrest is due entirely to GPR3 in the oocyte. Aim two is to investigate whether and how the presence of the somatic cells maintains the activities of Gs and GPR3 in follicle-enclosed oocytes at levels greater than those in isolated oocytes. Aim three is to investigate whether and how signals from the somatic cells decrease the activities of Gs and GPR3 during LH-induced reinitiation of meiosis. These studies will provide important new insights into the function of G-protein linked receptors in cell-cell signaling and cell cycle regulation. Ultimately, this knowledge concerning the regulation of the normal cell cycle may be applicable to treatment of pathological conditions in which cell cycle control is lost.